VASODILATOR EFFECTS OF ACETYLCHOLINE IN AN EXPERIMEN TAL MODEL OF HEART FAILURE

The purpose of the work presented here was to investigate endotheliumdependent relaxations in the rabbit coronary ligation model of heart failure. We investigated endothelium-dependent relaxations at the level of larger vessels (thoracic aorta and vena cava left renal artery and left renal vein lateral saphenous artery and lateral saphenous vein and finally central ear artery and marginal ear vein) in a model devised to mimic heart failure. The model presented here i s the rabbit coronary ligation model in which myocardial infarction was produced in male New Zealand white rabbits (2.6kg-3.0kg) by ligation of the marginal branch of the left descending coronary artery. The development of chronic heart failure was allowed to proceed over eight weeks. Animals were killed by overdose with pentobarbitone sodium (i.v. injection). Arteries and veins were carefully removed with as little connective tissue as possible and placed i n cold physiological salt solution (PSS). The arterial and venous rings were mounted in 10mL isolated organ baths, bathed in Krebs maintained at 37°C and gassed with 95% 02 plus 5% CO2 , The rings were then placed under different resting tensions. Acetylcholine (ACh) was chosen as endothelium-dependent vasodilator. After initial application of tension, tissues were left to equilibrate for a 60 min period. Then all tissues were precontracted with noradrenaline (1µM) nearly ten minutes before initial application of vasodilator. This induced submaximal contraction in all vessels with the exception of the ear vein. When the noradrenaline-induced contraction reached a plateau, cumulative concentration-response curves (CCRC) to acetylcholine were obtained by increasing the concentration in half-log increments. The results led to two major conclusions with respect to the model. First, the relaxation responses to acetylcholine were not impaired. Second, the results of our experiments in this model of heart failure suggest that normal stimulation of endothelial NO is preserved in peripheral conduit and capacitance vessels.